Abstract
Objectives
Type III Interferons, interleukin (IL)-29 and IL-28A, have been implicated in the inflammatory response of rheumatoid arthritis (RA). Increasing evidence suggests an important role of neutrophils in the pathogenesis of RA. However, the underlying mechanism remains unclear. Therefore, we investigated the expression of the receptor of these type III interferons, IL-28R1, on the neutrophils of RA patients, and further explored the roles of IL-29 and IL-28A on neutrophil activity.
Methods
Neutrophils were extracted from peripheral blood of patients who met the diagnostic criteria for RA and healthy controls. The serum levels of IL-29 and IL-28A in RA patients and healthy controls were examined by enzyme-linked immunoassay, and the expression of IL-28R1 on neutrophils was determined by flow cytometry. A transwell assay was performed to determine the chemotactic ability of IL-29 and IL-28A to neutrophils in RA patients.
Results
The serum IL-29 but not IL-28A levels were significantly elevated in RA patients, and neither was correlated with RA disease activity. IL-28R1 levels on neutrophils were significantly (p < 0.001) elevated in patients with RA (51.85% (36.10%, 67.03%)) compared with those of healthy controls (4.13% (3.54%, 7.96%)), and IL-29 and IL-28A had a significant chemotactic effect on neutrophils from the peripheral blood of RA patients.
Conclusion
IL-29 and IL-28A play an important role in regulating neutrophils which participate in the pathogenesis of RA. Therefore, inhibiting IL-29 and IL-28A may be a new therapeutic strategy for RA.
Key points • The IL-28R1 levels were increased in neutrophils of RA patients, suggesting its potentially important role in the pathogenesis of RA. • IL-29 and IL-28A induce the migration of neutrophils that participate in the development of RA. |
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References
Smolen Josef S, Daniel A, McInnes Iain B (2016) Rheumatoid arthritis. Lancet 388:2023–2038. https://doi.org/10.1016/S0140-6736(16)30173-8
Weinmann P, Moura RA, Caetano-Lopes JR, Pereira PA, Canhão H, Queiroz MV, Fonseca JE (2007) Delayed neutrophil apoptosis in very early rheumatoid arthritis patients is abrogated by methotrexate therapy. Clin Exp Rheumatol 25:885–887
Kotenko Sergei V, Grant G, Baurin Vitaliy V, Anita L-A, Shen M, Shah Nital K, Langer Jerome A, Faruk S, Harold D, Donnelly Raymond P (2003) IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 4:69–77. https://doi.org/10.1038/ni875
Paul S, Wayne K, Xu W, Katherine H, Stacy S et al (2003) IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 4:63–68. https://doi.org/10.1038/ni873
Robert S, Elizabeth W, Stefanie E, Kerstin W (2007) IL-19 and IL-20: two novel cytokines with importance in inflammatory diseases. Expert Opin Ther Targets 11:601–612. https://doi.org/10.1517/14728222.11.5.601
Daniel A, Tuhina N, Silman Alan J, Julia F, Felson David T et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581. https://doi.org/10.1002/art.27584
Wang F, Xu L, Xiaoke F, Guo D, Tan W, Miaojia Z (2012) Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis. Arthritis Res Ther 14:R228. https://doi.org/10.1186/ar4067
Wu Q, Yang Q, Hongsheng S, Ming L, Yuanchao Z, Antonio LC (2013) Serum IFN-λ1 is abnormally elevated in rheumatoid arthritis patients. Autoimmunity 46(1):40–43. https://doi.org/10.3109/08916934.2012.730587
Witte K, Gruetz G, Volk H-D, Looman A-C, Asadullah K, Sterry W, Sabat R, Wolk K (2009) Despite IFN-lambda receptor expression, blood immune cells, but not keratinocytes or melanocytes, have an impaired response to type III interferons: implications for therapeutic applications of these cytokines. Genes Immun 10:702–714. https://doi.org/10.1038/gene.2009.72
Xu L, Xiaoke F, Tan W, Weijuan G, Guo D, Miaojia Z, Wang F (2013) IL-29 enhances toll-like receptor-mediated IL-6 and IL-8 production by the synovial fibroblasts from rheumatoid arthritis patients. Arthritis Res Ther 15:R170. https://doi.org/10.1186/ar4357
Diana C-M, Maribel J, Mariana P, Araceli P, Felipe M, Amezcua-Guerra Luis M (2017) Type-III interferons and rheumatoid arthritis: correlation between interferon lambda 1 (interleukin 29) and antimutated citrullinated vimentin antibody levels. Autoimmunity 50(2):82–85. https://doi.org/10.1080/08916934.2017.1289181
You-Jung H, Seok CY, Ha KE et al (2018) Increased expression of interferon-λ in minor salivary glands of patients with primary Sjögren’s syndrome and its synergic effect with interferon-α on salivary gland epithelial cells. Clin Exp Rheumatol 112(3):31–40
Katrina B, Eames Hayley L, Miriam W, Byrne Adam J, Dany P, Pease James E, Sean D, Fiona MC, Williams Richard O, Udalova Irina A (2015) IFN-λ resolves inflammation via suppression of neutrophil infiltration and IL-1β production. J Exp Med 212:845–853. https://doi.org/10.1084/jem.20140995
Thomas David L, Thio Chloe L, Martin Maureen P et al (2009) Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461(7265):798–801. https://doi.org/10.1038/nature08463
Wright Helen L, Moots Robert J, Edwards Steven W (2014) The multifactorial role of neutrophils in rheumatoid arthritis. Nat Rev Rheumatol 10:593–601. https://doi.org/10.1038/nrrheum.2014.80
Wright Helen L, Moots Robert J, Bucknall Roger C, Edwards Steven W (2010) Neutrophil function in inflammation and inflammatory diseases. Rheumatology (Oxford) 49:1618–1631. https://doi.org/10.1093/rheumatology/keq045
Attila M (2013) Diverse novel functions of neutrophils in immunity, inflammation, and beyond. J Exp Med 210:1283–1299. https://doi.org/10.1084/jem.20122220
Irene P, Montserrat C, Barra Carolina M, He B, Linda C et al (2011) B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen. Nat Immunol 13:170–180. https://doi.org/10.1038/ni.2194
Wang X, Liang K-D, Jun-Ai Z et al (2018) Increased B cell activating factor is associated with B cell class switching in patients with tuberculous pleural effusion. Mol Med Rep 18:1704–1709. https://doi.org/10.3892/mmr.2018.9073
Andrew C, Theresa B, Bucknall Roger C, Edwards Steven W, Moots Robert J (2006) Neutrophil apoptosis in rheumatoid arthritis is regulated by local oxygen tensions within joints. J Leukoc Biol 80:521–528. https://doi.org/10.1189/jlb.0306178
Knight Jason S, Carmelo C-R, Kaplan Mariana J (2012) Proteins derived from neutrophil extracellular traps may serve as self-antigens and mediate organ damage in autoimmune diseases. Front Immunol 3:380. https://doi.org/10.3389/fimmu.2012.00380
Amariliz R (2019) Interferon Lambda’s new role as regulator of neutrophil function. J Interf Cytokine Res 39(10):609–617. https://doi.org/10.1089/jir.2019.0036
Kotenko Sergei V, Durbin Joan E (2017) Contribution of type III interferons to antiviral immunity: location, location, location. J Biol Chem 292:7295–7303. https://doi.org/10.1074/jbc.R117.777102
Vanessa E, Orchi D, Constance ME, Peicheng D, Yun-Juan C, Bryan C, Amy P, Ian W, Obar JJ, Durbin JE, Kotenko SV, Rivera A (2017) Type III interferon is a critical regulator of innate antifungal immunity. Sci Immunol 2:–16), undefined. https://doi.org/10.1126/sciimmunol.aan5357
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This study was approved by the institutional ethics committee of China-Japan Union Hospital of Jilin University. All patients gave written informed consent.
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Xu, Ts., Jia, Sy. & Li, P. Interleukin-29 and interleukin-28A induce migration of neutrophils in rheumatoid arthritis. Clin Rheumatol 40, 369–375 (2021). https://doi.org/10.1007/s10067-020-05211-3
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DOI: https://doi.org/10.1007/s10067-020-05211-3